Differential changes in ACh-, motilin-, substance P-, and K+-induced contractility in rabbit colitis

1999 ◽  
Vol 277 (1) ◽  
pp. G61-G68 ◽  
Author(s):  
Inge Depoortere ◽  
Gert van Assche ◽  
Theo Thijs ◽  
Karel Geboes ◽  
Theo L. Peeters

To test the hypothesis that the changes in intestinal contractility, which accompany inflammation of the gut, are agonist specific, we compared the response of inflamed strips to substance P (SP), motilin, ACh, and K+ as a function of time. In parallel experiments, changes in the general mechanical properties (passive tension, optimal stretch) of the colitic tissue were evaluated. Colitis was induced by trinitrobenzenesulfonic acid, and rabbits were killed after 1, 2, 3, 5, or 8 days. Passive tension was increased starting from day 2 until day 8, and maximal active tension ( T max) was generated at less stretch from day 5. A 50% decrease in T max was observed for ACh and K+ between days 2 and 3 and for motilin and SP between days 3 and 5. For all compounds, T max returned to normal after 8 days. The pEC50value (negative logarithm of the concentration that induces 50% of the maximal contractile activity) for ACh was increased from day 3 until day 8 and for SP at day 3, whereas for motilin it was decreased at day 1. The changes in passive tension and optimal stretch indicate generalized structural alterations of smooth muscle tissue. However, the different time profiles of the changes in active tension and contractile potency for different contractile agents suggest that inflammation specifically affects receptor-mediated mechanisms.

1988 ◽  
Vol 254 (1) ◽  
pp. G124-G129 ◽  
Author(s):  
D. L. Vermillion ◽  
S. M. Collins

We examined in vitro changes in contractility of jejunal longitudinal muscle strips in rats infected with the nematode parasite Trichinella spiralis. Length-passive tension relationships were unchanged. However, muscle from infected rats on days 5 and 6 postinfection (PI) generated maximal active tension induced by carbachol at significantly less stretch (39.9 +/- 1.0 and 34.3 +/- 6.3%, respectively) than control tissues (66.0 +/- 2.3%). In infected rats on day 5 PI, the maximum tension generated by carbachol (1.6 +/- 0.4 g/mm2) and by 5-hydroxytryptamine (5-HTP) (2.6 +/- 0.1 g/mm2) was significantly greater than in control tissue (0.5 +/- 0.2 g/mm2). On removal of calcium from the medium, responses of muscle from control and infected rats were reduced in a proportionate manner. The increased responsiveness to carbachol and 5-HTP was maximal by day 5 PI and was associated with a decrease in the ED50 value for 5-HTP but not for carbachol. All changes were reversed by 23 days PI. These results indicate that T. spiralis infection in the rat is associated with alterations in jejunal longitudinal smooth muscle function.


1996 ◽  
Vol 76 (4) ◽  
pp. 967-1003 ◽  
Author(s):  
A. Horowitz ◽  
C. B. Menice ◽  
R. Laporte ◽  
K. G. Morgan

Work performed with differentiated contractile smooth muscle tissue over the last two decades has made clear that covalent modification of myosin by phosphorylation of the 20-kDa myosin light chains is a significant mode of regulation of contractile activity in smooth muscle, particularly in regard to the generation of phasic contractions and the initial development of tonic contractions. This regulatory mechanism appears to be of unique importance in smooth muscle compared with striated muscle. It is equally clear, however, that there is an important role for protein kinase C in the regulation of smooth muscle tone maintenance, particularly in vascular smooth muscle. Several possible signal transduction cascades involving protein kinase C are outlined. Increasing evidence suggests a link between protein kinase C and actin-based regulatory mechanisms. This review places emphasis on relating up-to-date biochemical facts to the physiological realities of the smooth muscle cell.


2002 ◽  
Vol 80 (9) ◽  
pp. 865-871 ◽  
Author(s):  
Anabelle M. Opazo Saez ◽  
R Robert Schellenberg ◽  
Mara S Ludwig ◽  
Richard A Meiss ◽  
Peter D Paré

We have observed striking differences in the mechanical properties of airway smooth muscle preparations among different species. In this study, we provide a novel analysis on the influence of tissue elastance on smooth muscle shortening using previously published data from our laboratory. We have found that isolated human airways exhibit substantial passive tension in contrast to airways from the dog and pig, which exhibit little passive tension (<5% of maximal active force versus ~60% for human bronchi). In the dog and pig, airway preparations shorten up to 70% from Lmax (the length at which maximal active force occurs), whereas human airways shorten by only ~12% from Lmax. Isolated airways from the rabbit exhibit relatively low passive tension (~22% Fmax) and shorten by 60% from Lmax. Morphologic evaluation of airway cross sections revealed that 25-35% of the airway wall is muscle in canine, porcine, and rabbit airways in contrast to ~9% in human airway preparations. We postulate that the large passive tension needed to stretch the muscle to Lmax reflects the high connective tissue content surrounding the smooth muscle, which limits shortening during smooth muscle contraction by imposing an elastic load, as well as by causing radial constraint.Key words: isometric force, isotonic shortening, elastance.


1978 ◽  
Vol 74 (1) ◽  
pp. 197-210
Author(s):  
T. Tameyasu

1. The effect of the bathing solution tonicity on the mechanical properties of the anterior byssal retractor muscle (ABRM) of Mytilus edulis was examined. 2. The rate of relaxation of contracture tension produced by acetylcholine (ACh) was greatly reduced when the bathing solution tonicity was increased by adding NaCl, KCl or LiCl after the removal of ACh, whereas a decreased tonicity increased the rate of relaxation. 3. The contracted ABRM in hypertonic solutions showed no active shortening after an isotonic release and barely redeveloped active tension after a quick release. 4. The resistance to stretch increased with increasing tonicity of the bathing solution. 5. The wet weight of the ABRM decreased much more markedly in sucrose-hypertonic solution than in Na-, K- or Li-hypertonic solutions, but the decrease in the rate of relaxation was less marked in the former, indicating that there may be little relation between the rate of relaxation and the degree of osmotic deformation of the ABRM fibres. 6. It is suggested that the elevated ionic strength in the myoplasm may be related to a reduction in the rate of detachment of the cross-linkages between the thick and thin filaments.


2010 ◽  
Vol 298 (6) ◽  
pp. F1424-F1435 ◽  
Author(s):  
Paul H. Ratz ◽  
John E. Speich

Contraction of detrusor smooth muscle (DSM) at short muscle lengths generates a stiffness component we termed adjustable passive stiffness (APS) that is retained in tissues incubated in a Ca2+-free solution, shifts the DSM length-passive tension curve up and to the left, and is softened by muscle strain and release (strain softened). In the present study, we tested the hypothesis that APS is due to slowly cycling actomyosin cross bridges. APS and active tension produced by the stimulus, KCl, displayed similar length dependencies with identical optimum length values. The myosin II inhibitor blebbistatin relaxed active tension maintained during a KCl-induced contraction and the passive tension maintained during stress-relaxation induced by muscle stretch in a Ca2+-free solution. Passive tension was attributed to tension maintaining rather than tension developing cross bridges because tension did not recover after a rapid 10% stretch and release as it did during a KCl-induced contraction. APS generated by a KCl-induced contraction in intact tissues was preserved in tissues permeabilized with Triton X-100. Blebbistatin and the actin polymerization inhibitor latrunculin-B reduced the degree of APS generated by a KCl-induced contraction. The degree of APS generated by KCl was inhibited to a greater degree than was the peak KCl-induced tension by rhoA kinase and cyclooxygenase inhibitors. These data support the hypothesis that APS is due to slowly cycling actomyosin cross bridges and suggest that cross bridges may play a novel role in DSM that uniquely serves to ensure proper contractile function over an extreme working length range.


1988 ◽  
Vol 255 (6) ◽  
pp. G787-G793
Author(s):  
A. Merlo ◽  
S. Cohen

Mechanical properties and responses to neuropeptides were compared for proximal and distal feline colonic muscle. Proximal longitudinal (PL), proximal circular (PC), distal longitudinal (DL), and distal circular (DC) muscles were studied in vitro under isometric conditions. Total tension in DL [1.636 +/- 0.009 (SE) kg/cm2] was greater than in DC (0.699 +/- 0.004 kg/cm2) or PC (0.710 +/- 0.005 kg/cm2, P less than 0.05). Longitudinal muscle developed proportionately more active tension than circular muscle at each region (80.9% in DL vs. 54.1% in DC and 77.1% in PL vs. 52.3% in PC, P less than 0.01). Neuropeptides varied in potency and efficacy. Cholecystokinin octapeptide (CCK-8) was the most potent and efficacious in PL and substance P was the most efficacious in PC muscle (P less than 0.05). Substance P was more efficacious whereas CCK-8 and neurotensin were less efficacious in PC than PL muscle (P less than 0.01). DL muscle did not respond to CCK-8. DC muscle did not respond to CCK-8 or neurotensin. Isometric contractions to each neuropeptide were insensitive to tetrodotoxin. We conclude that 1) mechanical properties of circular and longitudinal colonic muscle differ and 2) responses to neuropeptides depend on anatomic region and intrinsic properties.


1987 ◽  
Vol 253 (6) ◽  
pp. G745-G750
Author(s):  
J. R. Herman ◽  
P. Bass

We determined length-stress properties and active tension development of rat jejunal longitudinal and circular muscle at various times after myenteric neuron ablation. Myenteric neurons were destroyed by serosal application of benzalkonium chloride. Active tension generation in response to both carbachol and barium was depressed in both muscle layers up to 7 days after treatment, at which times the responses were normal. At 15 days, circular muscle responses were still comparable to control, but longitudinal muscle responses were significantly increased. Length-stress parameters of circular muscle were minimally affected, while those of longitudinal muscle were significantly altered 15 and 30 days after treatment. These alterations include changes in resting stress and increased active stress generation at both times. Our results suggest that 1) normal myenteric innervation is necessary for normal contractile activity in rat jejunal smooth muscle and 2) changes in cellular or tissue morphology or alterations in intracellular calcium homeostasis, as seen in other tissue, may occur after myenteric plexus ablation.


2004 ◽  
Vol 287 (6) ◽  
pp. L1165-L1171 ◽  
Author(s):  
Xueyan Zheng ◽  
Danyi Zhou ◽  
Chun Y. Seow ◽  
Tony R Bai

Induction of hypertrophy and inhibition of apoptosis may be important mechanisms contributing to increased airway smooth muscle (ASM) mass in asthma. Data from our laboratory indicate that cardiotrophin-1 (CT-1) induces hypertrophy and inhibits apoptosis in isolated human ASM cells. To determine whether these novel effects of CT-1 also occur in the airway tissue milieu and to determine whether structural changes are accompanied by functional changes, matched pairs of guinea pig airway explants were treated with or without CT-1 for 7 days, and structural features as well as isometric and isotonic contractile and relaxant mechanical properties were measured. CT-1 (0.2–5 ng/ml) increased both myocyte mass and extracellular matrix in a concentration-dependent fashion. CT-1 (10 ng/ml)-treated tissues exhibited a significant increase in passive tension at all lengths on day 7; at optimal length, passive tension generated by CT-1-treated tissues was 1.72 ± 0.12 vs. 1.0 ± 0.1 g for control. Maximal isometric stress was decreased in the CT-1-treated group on day 7 (0.39 ± 0.10 kg/cm2) vs. control (0.77 ± 0.15 kg/cm2, P < 0.05). Isoproterenol-induced relaxant potency was reduced in CT-1-treated tissues, log EC50 being −7.28 ± 0.34 vs. −8.12 ± 0.25 M in control, P < 0.05. These data indicate that CT-1 alters ASM structural and mechanical properties in the tissue environment and suggest that structural changes found in the airway wall in asthma are not necessarily associated with increased responsiveness.


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